Inhibition of miR-361-5p suppressed pulmonary artery smooth muscle cell survival and migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway

MicroRNAs play a crucial role in the progression of pulmonary arterial hypertension (PAH). The aim of this study was to investigate the effect of miR-361-5p on the proliferation, migration and apoptosis of pulmonary artery smooth muscle cells (PASMCs) that under the treatment of hypoxia and explore...

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Veröffentlicht in:Experimental cell research 2018-02, Vol.363 (2), p.255-261
Hauptverfasser: Zhang, Xiaoping, Shao, Runxia, Gao, Weiwei, Sun, Guanghao, Liu, Ying, Fa, Xian’en
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Sprache:eng
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Zusammenfassung:MicroRNAs play a crucial role in the progression of pulmonary arterial hypertension (PAH). The aim of this study was to investigate the effect of miR-361-5p on the proliferation, migration and apoptosis of pulmonary artery smooth muscle cells (PASMCs) that under the treatment of hypoxia and explore the underlying mechanisms. The results proved that hypoxia noticeably up-regulated the expression of miR-361-5p in PASMCs in comparison to the normoxia-treated cells, while TNF-α and IL-6 stimulation had no obvious effects on miR-361-5p level. Hypoxia induced miR-361-5p elevation in a HIF-1α-dependent manner. Inhibition of miR-361-5p dramatically inhibited hypoxia-induced cell proliferation and migration. miR-361-5p inhibition also rescued hypoxia exposure caused suppression of PASMCs apoptosis. In addition, the results showed that ABCA1 was a direct target of miR-361-5p and was down-regulated in hypoxia-induced PASMCs. Hypoxia and TNF-α or IL-6 stimulation significantly inhibited ABCA1 expression. In addition, overexpression of ABCA1 enhanced the effect of miR-361-5p on hPASMCs. Furthermore, the inhibition of miR-361-5p significantly down-regulated the expression level of p-JAK2 and p-STAT3. In conclusion, it may suggest that the suppression of miR-361-5p suppressed PASMC survival and migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway. •MiR-361-5p was significantly increased in hypoxia-induced hPASMCs.•Inhibition of miR-361-5p suppressed hypoxia-induced hPASMCs proliferation and migration.•miR-361-5p targeted ABCA1.•Overexpression of ABCA1 enhanced the effect of anti-miR-361-5p on hPASMCs proliferation and migration.•miR-361-5p inhibited JAK2/STAT3 pathway.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2018.01.015